In an ongoing effort to fight disease by manipulating energy regulatio...The study published in the August 12 issue of the Journal of Biologic... A cell's energy level is critical to its survival explains Witters... We decided to work with cervical and lung cancer cells because LKB1 i... With the addition of these two kinases we think we have all nearly t...

In an ongoing effort to fight disease by manipulating energy regulation of cells, a collaborative study led by Dartmouth Medical School (DMS) has demonstrated that cells lacking a tumor-suppressing kinase called LKB1 can still maintain healthy energy levels when they become stressed. This energy regulation is essential for keeping cells from dying off too quickly. The study's results could signal new advances for combating cancerous tumor growth, but also type 2 diabetes and obesity.

The study, published in the August 12 issue of the Journal of Biological Chemistry (JBC), was headed by Dr. Lee Witters, Eugene W. Leonard 1921 Professor of Medicine and Biochemistry at DMS and of Biological Sciences at Dartmouth College, who has researched kinases for over 25 years. Kinases encompass a large family of enzyme proteins that play key roles in the workings of most animal cells. He has focused much of his research on the AMP-activated kinase (AMPK) which responsible for managing energy within cellular pathways.

"A cell's energy level is critical to its survival," explains Witters, who likens a low-energy cell to a car with no gas in its tank. "In a previous study, we found that the cellular "gas gauge," AMPK, can turn around and alter any deficits in the cell if it is turned on by the kinase LKB1. In this JBC study, we wanted to see if AMPK could also be turned on by something besides LKB1."

"We decided to work with cervical and lung cancer cells because LKB1 is absent from the cellular pathway," said Rebecca Hurley, lead author of the study and a graduate student in the Molecular and Cellular Biology Program at Dartmouth. Working closely with scientists at St. Vincent's Institute in Australia and Duke University, the DMS team concluded that two kinases in these cancer cells, CaMKKα and CaMKKβ, are able to regulate AMPK independent of LBK1.

"With the addition of these two kinases, we think we have all nearly the players re
sponsible for energy regulation within the cell, which should offer new opportunities in cancer treatment," said Hurley. "If we can stifle a cancer cell's ability to adapt to an energy deficit, it might lose its growth advantage." "You need to know how all these proteins interact before you can make truly significant advances," echoes Witters "It's like poker; not only do you need to know what each card signifies individually, but you must have an understanding of how they play off each other in order to win."

In addition to cancer-fighting potential of AMPK regulation, the enzyme also responds to changes in insulin or glucose and mediates impaired energy metabolism, a hallmark of type 2 diabetes. "This indicates that AMPK is a very tempting target for the treatment of some forms of diabetes and even obesity," said Witters.

As Witters' laboratory continues to zero in on the central role of kinases in the treatment of disease, he acknowledges that this research is becoming more complex and multiple approaches are needed to find solutions. Witters believes that significant breakthroughs in science can only be achieved through open collaboration, citing partnerships between faculty and students, and between other institutes outside the Dartmouth community.

Often referring to his laboratory as a classroom, Witters pointed out the integral roles played by Hurley and Dartmouth College undergraduate student Jeanne Franzone '05, a co-author of the study. "Students are the grand integrators of collaboration," he said, noting that Hurley traveled to other labs in the US to complete this study. Other co-authors of the study are Kristin Anderson and Anthony Means from Duke University and Bruce Kemp from The St. Vincent's Institute and CSIRO Health Sciences and Nutrition in Australia.

(Date:3/29/2017)... , March 29, 2017 higi, the health IT ... North America , today announced a ... the acquisition of EveryMove. The new investment and acquisition ... of tools to transform population health activities through the ... data. higi collects and secures data today ...

(Date:3/24/2017)... -- Research and Markets has announced the addition of ... - Industry Forecast to 2025" report to their offering. ... The Global Biometric Vehicle ... around 15.1% over the next decade to reach approximately $1,580 million ... estimates and forecasts for all the given segments on global as ...

(Date:9/22/2017)... ... September 22, 2017 , ... The Academy of ... October 28 and 29, 2017, to promote AMA’s programs, member services, and the ... different hobbies, including but not limited to model aviation and other RC activities. ...

(Date:9/21/2017)... ... September 21, 2017 , ... ... portal. Each relaunch of the portal includes new features that facilitate streamlined and ... companies seek to remain at the forefront of medical advancements, they rely on ...

(Date:9/21/2017)... ... September 21, 2017 , ... ... the election of Paul Hermes, Entrepreneur in Residence at Medtronic, Inc., to serve ... developed a proprietary, tissue-engineered scaffold for anterior cruciate ligament (ACL) reconstruction that is ...